Abstract
Yersinia pestis, the etiologic agent of plague, is one of the deadliest pathogens in the modern world. Y. pestis achieves its virulence in a biphasic manner promoting anti-inflammatory responses during early stage of infection and inducing pro-inflammatory responses during late disease. Multiple host signaling pathways are involved in combating this highly pathogenic bacterium. To understand the molecular mechanisms that are disrupted by Y. pestis during infection, we have been studying major pathways of activation of innate and adaptive immunity induced by toll-like receptor (TLR) and non-TLR signaling pathways, resulting in activation of NFκB or interferons. We found a central role for inflammatory mediators signal transducer and activator of transcription 1 and interferon response factor 3 but not NFκB or adaptive immune cells in mediating host defense against infection. Together, the data reveal delicate intricacies between proliferation of the pathogen within the host and involvement of multiple inflammatory pathways during Y. pestis infection.
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Acknowledgements
We are indebted to Drs. Michael Diamond and Herbert Virgin IV for their generosity in providing the knockout mice. We are also grateful to members of our laboratory for assistance with the BSL3 experiments and helpful discussions. Histology services were provided by the Research Animal Diagnostic Laboratory (RADIL) at the University of Missouri. This work was supported by the NIH/NIAID Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (U54157160).
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Patel, A.A., Anderson, D.M. (2012). Innate Immune Responses During Infection with Yersinia pestis . In: de Almeida, A., Leal, N. (eds) Advances in Yersinia Research. Advances in Experimental Medicine and Biology, vol 954. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3561-7_19
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